Enhanced osteoinductive capacity of poly(lactic-co-glycolic) acid and biphasic ceramic scaffolds by embedding simvastatin.

OBJECTIVES: This study evaluated the effect of embedding simvastatin (SIM) on the osteoinductive capacity of PLGA + HA/ßTCP scaffolds in stem cells from human exfoliated deciduous teeth (SHED). MATERIALS AND METHODS: Scaffolds were produced by PLGA solvent dissolution, addition of HA/ßTCP, solvent evaporation, and leaching of sucrose particles to impart porosity. Biphasic ceramic particles (70% HA/30% ßTCP) were added to the PLGA in a 1:1 (w:w) ratio. Scaffolds with SIM received 1% (w:w) of this medication. Scaffolds were synthesized in a disc-shape and sterilized by ethylene oxide. The experimental groups were (G1) PLGA + HA/ßTCP and (G2) PLGA + HA/ßTCP + SIM in non-osteogenic culture medium, while (G3) SHED and (G4) MC3T3-E1 in osteogenic culture medium were the positive control groups. The release profile of SIM from scaffolds was evaluated. DNA quantification assay, alkaline phosphatase activity, osteocalcin and osteonectin proteins, extracellular calcium detection, von Kossa staining, and X-ray microtomography were performed to assess the capacity of scaffolds to induce the osteogenic differentiation of SHED. RESULTS: The release profile of SIM followed a non-liner sustained-release rate, reaching about 40% of drug release at day 28. Additionally, G2 promoted the highest osteogenic differentiation of SHED, even when compared to the positive control groups. CONCLUSIONS: In summary, the osteoinductive capacity of poly(lactic-co-glycolic) acid and biphasic ceramic scaffolds was expressively enhanced by embedding simvastatin. CLINICAL RELEVANCE: Bone regeneration is still a limiting factor in the success of several approaches to oral and maxillofacial surgeries, though tissue engineering using mesenchymal stem cells, scaffolds, and osteoinductive mediators might collaborate to this topic.

Rehabilitation Challenge in Patient With a High Smile Line: Case Report and Review of Surgical Protocols.

INTRODUCTION: Defects in the maxillary anterior teeth are delicate and difficult to solve because of the esthetic, functional, and psychological impairment that may arise if the rehabilitation treatment does not return the damaged tissues to the naturalness. Esthetic predictability and reduced surgical interventions are some great reasons to simplify dental treatments. During the presurgical evaluation, the clinician should review the implant esthetic risk profile, considering the patient's smile line, the esthetic demands, the hard and soft tissue thickness and width, and the gingival biotype. Thus, achieving long-term esthetic results initiates with a detailed case planning before surgical intervention. CASE PRESENTATION: The present report described a complex esthetic clinical case involving teeth and dental implant related to a high smile line. The clinical case was solved through immediate implant placement and immediate loading using a personalized prosthetic abutment and finalized with the installation of metal-free prosthetic restorations. CONCLUSION: The use of a personalized prosthetic abutment helped to achieve a better emergence of the prosthesis under the periodontal tissues. Although it was a challenging esthetic case, especially because of the high smile line, the result was a natural smile while the adjacent soft tissues maintained their esthetics and health.

Titanium coated with poly(lactic-co-glycolic) acid incorporating simvastatin: Biofunctionalization of dental prosthetic abutments.

OBJECTIVE: To propose a biofunctionalized prosthetic abutment by analyzing physico-chemical and morphological properties, simvastatin (SIM) release, and biocompatibility of titanium (Ti) disks coated with poly(lactic-co-glycolic) acid (PLGA) incorporating SIM. METHODS: Titanium disks (8 × 3 mm) were distributed into four groups: Ti: pure Ti; Ti + PLGA: Ti coated with PLGA; Ti + PLGA + SIM6%: Ti + PLGA with 6% SIM; and Ti + PLGA + SIM0.6%: Ti + PLGA incorporating 0.6% SIM. PLGA was prepared through chloroform evaporation technique. After complete dissolution of PLGA, SIM was diluted in the solution. Ti + PLGA, Ti + PLGA + SIM6%, and Ti + PLGA + SIM0.6% were dip coated with PLGA and PLGA + SIM, respectively. Samples were sterilized by ethylene oxide. For SIM release assay, disks were submerged in PBS, pH 7.4, 37°C, 30 rpm up to 600 hours. At different time intervals, SIM was quantified by spectrophotometry (238 nm). For characterization of the biomaterial components, it was performed Fourier-transform infrared spectroscopy, differential scanning calorimetry, scanning electron microscopy (SEM), optical profilometry, and atomic force microscopy. Biocompatibility analyses were performed by MTS colorimetric assay on murine fibroblasts L929, human gingival fibroblasts (HGFs), and stem cells from human exfoliated deciduous teeth (SHEDs). Absorbance was measured at 490 nm, and percentages of viable cells were calculated in relation to positive control (Ti). SEM images were obtained to verify cell adhesion and morphology. One-way ANOVA followed by Tukey's post hoc test was applied (P < 0.05) for statistical analyses. RESULTS: SIM release was slow and continuous, reaching about 21% of the incorporated SIM after 600 hours. Topographical analyses revealed success in coating Ti disks with PLGA incorporating SIM. Regarding biocompatibility test, Ti + PLGA + SIM0.6% showed the highest percentage of L929 viability at days 3 and 7. There was no significant difference for Ti, Ti + PLGA, and Ti + PLGA + SIM0.6% groups on cell viability of both SHEDs and HGFs at days 3 and 7. SEM corroborates that SHEDs and HGFs were able to adhere and proliferate on Ti, Ti + PLGA, and Ti + PLGA + SIM0.6% surfaces. CONCLUSION: A slow and controlled release of SIM was achieved, attributed to a diffusional mass transfer mechanism. Moreover, a homogenous coating topography was obtained. Additionally, 0.6% SIM incorporated into PLGA coating improved fibroblasts L929 viability compared to titanium or PLGA. Also, 0.6% SIM incorporated into PLGA promoted cell viability of about 100% for HGFs and approximately 150% for human mesenchymal stem cells. Therefore, this study allows to consider the use of PLGA-coated titanium incorporating SIM as a biofunctionalized abutment for dental implants.

Solid dispersions enhance solubility, dissolution, and permeability of thalidomide.

Thalidomide (THD) is a BCS class II drug with renewed and growing therapeutic applicability. Along with the low aqueous solubility, additional poor biopharmaceutical properties of the drug, i.e. chemical instability, high crystallinity, and polymorphism, lead to a slow and variable oral absorption. In this view, we developed solid dispersions (SDs) containing THD dispersed in different self-emulsifying carriers aiming at an enhanced absorption profile for the drug. THD was dispersed in lauroyl macrogol-32 glycerides (Gelucire® 44/14) and α-tocopherol polyethylene glycol succinate (Kolliphor® TPGS), in the presence or absence of the precipitation inhibitor polyvinylpyrrolidone K30 (PVP K30), by means of the solvent method. Physicochemical analysis revealed the formation of semicrystalline SDs. X-ray diffraction and infrared spectroscopy analyses suggest that the remaining crystalline fraction of the drug in the SDs did not undergo polymorphic transition. The impact of the solubility-enhancing formulations on the THD biopharmaceutical properties was evaluated by several in vitro techniques. The developed SDs were able to increase the apparent solubility of the drug (up to 2-3x the equilibrium solubility) for a least 4 h. Dissolution experiments (paddle method, 75 rpm) in different pHs showed that around 80% of drug dissolved after 120 min (versus 40% of pure crystalline drug). Additionally, we demonstrated the enhanced solubility obtained via SDs could be translated into increased flux in a parallel artificial membrane permeability assay (PAMPA). In summary, the results demonstrate that SDs could be considered an interesting and unexplored strategy to improve the biopharmaceutical properties of THD, since SDs of this important drug have yet to be reported.